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Biomedical subjects

C Tan

Publications and source records attributed to C Tan.

At least 37 records · Page 2Linked to original sources
PubMed1997

The internal ribosomal entry site of the encephalomyocarditis virus enables reliable coexpression of two transgenes in human primary T lymphocytes.

It is essential for the improvement of adoptive cell therapies to generate efficiently large populations of human primary T cells that reliably express a suicide gene conferring drug sensitivity, such as herpes simplex virus thymidine kinase (HSVtk). We show here that an optimized dicistronic vector containing the encephalomyocarditis virus (EMCV) internal ribosomal entry site (IRES) is functional in human primary. T lymphocytes that bear on average one integrated vector copy per cell. We demonstrate reliable coexpression of the marker NTP, an inactive mutant of the human low-affinity nerve growth factor receptor and HSVtk. In the dicistronic vector NIT, NTP is expressed as a cap-dependent marker and HSVtk as a nonselectable IRES-dependent gene. Cell-surface expression of NTP is sufficient to allow for the efficient and rapid enrichment of the transduced cells to high purity. Of these purified lymphocytes, 97 +/- 4% and 92 +/- 6% are selectively eliminated when cultured in the presence of 1.0 or 0.1 microM ganciclovic respectively, establishing that the EMCV IRES ensures efficient and sufficient expression of two genes in human primary T cells.

Animals↗
PubMed1997

[CT for diagnosis of parathyroid adenoma].

We analyzed Ct findings of 10 cases with parathyroid adenoma which had been verified by surgery and pathologic section. The correct localization of 9 adenomas was made by CT preoperatively. The method of CT scanning of parathyroid adenoma were elucidated. The results showed that most adenomas were located in the groove between trachea and esophagus. The contour of tumors was oval, the edge was smooth and regular. Enhancement CT images were helpful for differentiating the tumor from blood vessel. It is indicated that CT scanning is a good method for localizing the parathyroid adenoma.

Adenoma↗
PubMed1997

[Kaposi's sarcoma associated with HIV in otorhinolaryngology: report of 21 cases].

Twenty one cases of kaposi's sarcoma (KS) with manifestation in the field of otolaryngology are reported. The incidence of KS is increasing following epidemic of AIDS all over the world. Epistaxis, nasal obstruction, sore-throat, dry of foreign body filling in throat and nodal mass are most frequent manifestation. The relationship of KS with HIV, it's pathology and diagnosis are discussed.

Adolescent↗
PubMed1996

412-positive mesodermal cells and the gonadal mesoderm are separate from the fat-cell lineage.

The Drosophila retrotransposon, 412, is expressed in a cell-specific manner during embryogenesis. At stage 11, 412 transcripts are present in bilateral clusters of cells within the mesoderm. The posterior clusters of 412-positive cells become associated with the gonads at stage 13; however, the fate of the cells in the remaining clusters is unknown. We have tested by in situ hybridization to whole-mount embryos the possible identity of these cells with known precursor cell types present in bilateral clusters. We simultaneously located the 412-positive cells and the precursor cells to visceral muscle or the fat body. We have determined that the 412-positive cells do not correspond to these precursor cells and that the development of the visceral muscle or fat body does not affect the expression of 412 during embryogenesis.

Adipocytes↗
PubMed1996

Mechanism and structure based inhibitors of phospholipase C enzymes.

PI-specific PLC enzymes are a key component of phosphatidylinositol-mediated signaling pathways since the hydrophobic product, diacylglycerol, activates protein kinase C and the water-soluble product, inositol trisphosphate, is involved in Ca2+ mobilization. Nonspecific, or PC-PLC, enzymes can generate diacylglycerol without Ca2+ mobilization. A series of inhibitors, both lipophilic and water-soluble, have been synthesized to target each of these two classes of PLC enzymes. Design of the inhibitors was based on proposed enzyme mechanisms and available crystal structures. The solution conformations of the lipophilic phospholipid analogs, (diheptanoylphosphatidyl(2-O-methyl)inositol for PI-PLC and a dihexanoyl-sn-(3-N-benzylaminoglycero)phosphoramidocholine for PC-PLC, have been determined using NMR methodology and the interaction of these compounds with bacterial enzymes has been examined. Water-soluble inhibitors include strained cyclic phosphonates for PI-PLC and vanadate for PC-PLC. An eventual goal of this work is to generate compounds that specifically target each type of intracellular PLC activity.

Bacillus cereus↗
PubMed1996

Growth and final height after treatment for childhood Hodgkin disease.

PURPOSE: To evaluate in children the impact of contemporary treatment for Hodgkin disease on the pattern of growth and final height. PATIENTS AND METHODS: We studied 80 patients (54 males) aged <14 years at diagnosis, with newly diagnosed, pathologically confirmed Hodgkin disease, treated at a single institution. Forty six patients received chemotherapy (CT) + radiotherapy (RT), 23 patients received RT alone, and 11 patients received CT alone. Heights were obtained at diagnosis, at the end of treatment, 1, 2, and 3 years after the end of treatment and at attainment of final height. Heights were converted to age- and sex-adjusted SD scores (SDS). RESULTS: There was a significant change in height SDS at the end of treatment compared to height SDS at diagnosis for all three groups (CT + RT: -0.33, p<0.001; RT: +0.09, p=0.027; CT: -0.24, p=0.012). Over the 3 years following treatment, the rate of change of height SDS was not statistically different between the three treatment groups. Final height SDS was decreased for patients receiving RT + CT (-0.41 SDS, p=0.02; n=31). The change in final height SDS for patients receiving RT or CT only was -0.36 (n=14) and +0.42 (n=4), respectively. Loss of final height SDS correlated with younger age at diagnosis (p=0.005). Patients receiving higher RT doses tended to fare worse (p=0.08). CONCLUSIONS: Pediatric patients treated for Hodgkin disease with the combination of RT and CT suffer a small but significant decrease in their final height SDS. Younger patients and those treated with higher RT doses appear to experience the greatest loss of height potential.

Adolescent↗
PubMed1996

Trabeculectomy--success rates in a Singapore hospital.

Previously published papers on the success of trabeculectomy as a treatment for glaucoma show success rates between 67% and 84%. The success rate of trabeculectomy in Afro-Carribean patients was observed to be lower than in Caucasian patients. It has been commonly believed that the success rate of trabeculectomy in Oriental/Asian eyes would lie somewhere between these. We reviewed the records of 51 consecutive trabeculectomies performed in the National University Hospital, Singapore and found that our success rate was lower-43.1% overall and 48.7% for primary glaucomas.

Adult↗
PubMed1995

Amplification of the dihydrofolate reductase gene is a mechanism of acquired resistance to methotrexate in patients with acute lymphoblastic leukemia and is correlated with p53 gene mutations.

Although dihydrofolate reductase (DHFR) gene amplification is a common mechanism of resistance to methotrexate (MTX) in tumor cell lines, with the exception of a few case reports, the incidence of this phenomenon as a mechanism of MTX resistance in the clinic has not been reported. We studied 38 untreated patients and 29 patients in relapse with acute lymphoblastic leukemia (ALL) for gene amplification and p53 gene mutations. Three patients were studied both at diagnosis and at each of two relapses after treatment with MTX. Nine of 29 relapsed patients (31%) had low-level DHFR gene amplification (two to four gene copies) associated with increased levels of DHFR mRNA and enzyme activity. Of significance was a correlation of gene amplification with p53 mutations in seven of nine relapsed patients (P < .001). Low-level DHFR gene amplification may be an important cause of MTX resistance in ALL and strengthens the concept that mutations in the p53 gene may lead to gene amplification as a consequence of defective cell cycle control.

Adolescent↗
PubMed1995

Lead-induced nephropathy: relationship between various biological exposure indices and early markers of nephrotoxicity.

Lead nephropathy in adults is silent and insidious, characterized by the absence of proteinuria in its early phase. Of the early markers of nephrotoxicity, urinary N-acetyl-beta-D-glucosaminidase (NAG) appears to be the only one that is elevated in early lead nephropathy. However, the elevation in urinary NAG activity may be a response to a sharp increase in renal burden of lead. Its usefulness as a marker of chronic lead nephropathy is thus in doubt. There is a need, then, to identify a reliable early biological indicator of lead-induced kidney damage. Furthermore, there is also a need to identify suitable markers of chronic exposure to describe meaningful dose-response and dose-effect relationships. Traditionally, blood lead (PbB) was used, but the current blood lead level (PbBrec) is more an indicator of recent exposure. Time-integrated blood lead indices (PbBint) derived from repeated serial PbB measurements can be used as indices of chronic exposure. In 128 lead-exposed workers, the PbBint was the most important exposure variable in describing the variability in urinary alpha 1-microglobulin (U alpha 1 m), urinary beta 2-microglobulin (U beta 2m), and urinary retinol binding protein (URBP). U alpha 1m was the only marker that was significantly higher in the exposed group, with a good dose-response and dose-effect relationship with PbBint. The lack of dose-response and dose-effect relationships in other studies may be due to inappropriate exposure markers as well as less sensitive response markers. PbBint has a better correlation than PbBrec. Furthermore, U alpha 1m may be the most sensitive of the markers because of its higher molecular weight.

Adolescent↗
PubMed1995

Cardiac failure and dysrhythmias 6-19 years after anthracycline therapy: a series of 15 patients.

The clinical course of late symptomatic anthracycline cardiomyopathy, and resultant changes of cardiac function, were described in 15 patients. They represented a subset of 300 patients who had cardiac evaluations to identify the prevalence of late cardiotoxicity more than 4 years after anthracycline therapy in these patients. The clinical course and all available cardiac evaluations including electrocardiography, continuous taped electrocardiography, echocardiography, radionuclide cardiac angiography, cardiac catheterization, and endomyocardial biopsy, of the 15 patients were reviewed. The patients had received 285-870 (median 540) mg/M2 of daunorubicin and/or doxorubicin 6-19 (median 12) years prior to the onset of late symptoms. Seven patients also had 2,100-4,000 cGy mediastinal radiotherapy. Five patients had required treatment for cardiac symptoms at the end of chemotherapy but 10 patients had no cardiac problems anteceding their late decompensation. Fractional shortening on echocardiogram at late decompensation was 8-20% (median 17%) and radionuclide left ventricular ejection fraction was 8-59% (median 38%). All were treated with digitalis and diuretics and 13/15 with afterload reduction, with at least transient improvement of symptoms. They were followed for 1-9 (median 3) years after late decompensation. One died of uncontrollable cardiac failure. Another underwent successful cardiac transplantation. Conduction abnormalities and dysrhythmias were present in 14/15 patients and 3 died suddenly. Two more had syncope, one requiring an automatic cardiac defibrillator. Endomyocardial biopsy or autopsy revealed hypertrophy and fibrosis in 10/10 patients. Our patients with early cardiac symptoms improved transiently but decompensated later and patients with no early symptoms developed cardiac symptoms more than 10 years after anthracycline therapy. Therefore, patients who have received anthracyclines should have continued cardiac evaluation.

Adolescent↗
PubMed1995

Glomerular function of lead-exposed workers.

Among lead-exposed workers, there is evidence of increased mortality from chronic renal diseases (nephritis and nephrosis). Epidemiological studies using early markers of nephropathy among lead-exposed workers failed to demonstrate early renal changes. This study is aimed at assessing the glomerular function of 137 lead-exposed subjects and at evaluating whether changes in markers of glomerular function are related to exposure indices derived from longitudinal blood lead data. A control group of 153 postal workers was also investigated. Several exposure indices were derived for the exposed workers, including a time-integrated index Pb in blood (PbB)int and the number of times the PbB was above critical values (PbB400, PbB500, PbB600). Through multiple linear regression analysis, PbBint was the best predictor of variation in serum beta 2-microglobulin (S beta 2m) and alpha 1-microglobulin (S alpha 1m) and urinary albumin (UA1b). A small but statistically significant difference in the mean beta 2m was found. S beta 2m was also the only marker showing a significantly higher prevalence rate ratio (PRR) of abnormalities among lead-exposed workers. Though there was no clear dose-response relationship with PbBint as the index of dose, all the 15 subjects with abnormal S beta 2m in the older age group were found in the highest PbBint group. Furthermore, of the 8 subjects with low 4-h creatinine clearance (CrCl4h), 6 had abnormal levels of beta 2m. Two subjects with CrCl4h of less than 75 ml/min/1.74 m2 had high PbBint values, thus suggesting that high blood lead levels over a prolonged time may be associated with decreased CrCl4h. Though the long-term significance of elevated S beta 2m and UA1b is unclear, their association with high PbBint and decreasing CrCl4h indicate a potentially adverse effect. Their relationship with PbB400 and PbB600 suggests that the threshold of 700 micrograms/l for PbB may not prevent the occurrence of lead nephropathy.

Adolescent↗
PubMed1995

Molecular characterization of a lipid-modified virulence-associated protein of Rhodococcus equi and its potential in protective immunity.

Virulent strains of Rhodococcus equi produce plasmid-mediated 15- and 17-kDa proteins, which are thermoregulated and apparently surface-expressed. We demonstrated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) that R. equi produce three antigenically-related virulence-associated proteins, a diffuse 18-22-kDa, a 17.5-kDa and a 15-kDa protein. Phase partitioning of whole cells of R. equi strain 103 with Triton X-114 (TX-114) and labelling with [3H]-labelled palmitic acid showed that the two higher molecular weight proteins are hydrophobic and lipid modified. The 15-kDa protein did not partition into TX-114 and was not lipid modified. Cloning and expression of a fragment of the R. equi virulence plasmid in Escherichia coli showed that the three proteins were expressed from a single gene. Sequence analysis of this gene (designated vapA) revealed a 570-bp open reading frame encoding a polypeptide of 189 amino acids with a calculated molecular mass of 19,175 Da. The mature, nonlipid modified protein had a calculated mass of 16,246 Da. The 17.5- and 18-22-kDa forms of the protein are therefore due to lipid modification. No significant sequence homology of the vapA gene with other reported nucleotide sequences were found. Opsonization of virulent R. equi with an IgG1 mouse monoclonal antibody (MAb103) to the VapA protein significantly enhanced uptake in the murine macrophage cell line IC-21. Intraperitoneal injection of mice with Mab103 enhanced initial clearance from the liver of mice challenged intravenously with R. equi. Immunization of mice with the lipid-modified VapA purified by SDS-PAGE fractionation or with acetone precipitated VapA protein following TX-114 extraction resulted in significantly enhanced clearance from the liver and spleen following intravenous challenge. The VapA protein of R. equi appears therefore to be a protective immunogen.

Actinomycetales Infections↗
PubMed1995

Paediatric pacemaker implant using the transvenous endocardial approach.

The advent of the pacemaker has opened a whole new dimension to management in cardiology. Although its use has been well described in adults, its role in paediatric cardiology has proven to be equally exciting and challenging. We describe a case of a child with complex cyanotic heart disease who had an insertion of a cardiac pacemaker via the transvenous route, one of the youngest to be performed locally. This article also highlights the pertinent features of paediatric pacemaker therapy, including its indications and implantation technique.

Child↗
PubMed1994

Selective transfer of cholesteryl ester over triglyceride by human plasma lipid transfer protein between apolipoprotein-activated lipid microemulsions.

The substrate-specific rate of the human plasma lipid transfer protein (LTP) reaction was studied using pyrene-labeled substrate lipid analogues as probes for various lipids, by monitoring the ratio of the fluorescence intensities of their excimers to those of their monomers as an indicator of pyrene concentration in the microenvironment. Transfer of cholesteryl ester (CE) and triglyceride (TG) was demonstrated between human high-density lipoproteins, between low-density lipoproteins, and between these two lipoprotein, and the specific fractional transfer rate of CE was always higher than that of TG by a factor of 2.4-7.9. On the other hand, the transfer by LTP of CE, TG, and phosphatidylcholine (PC) was also demonstrated between lipid microemulsions having an average diameter of 25-26 nm using the same probes, but only when the emulsions were activated by apolipoproteins A-I, A-II, E, or C-III. The maximally activated rates of the transfer of CE and TG were the same when measured between the emulsions with cores composed exclusively of either lipid. The specific fractional transfer rate of pyrene-CE, however, was inversely proportional to the percentage of CE in the TG core of the emulsions, and the initial transfer of TG was almost completely inhibited by the presence of small percentages of CE in the TG core. Thus, the transfer of CE between the emulsions is highly selective over that of TG by orders of magnitude, much more selective than the reaction between any natural plasma lipoproteins, but this selectivity is not a rate-limiting step of the overall LTP reaction. The maximally activated LTP-catalyzed transfer rate of PC between the emulsions was somewhat higher than that of CE or TG and was not affected by the composition of the core lipids of the emulsion, TG or CE. When an excess amount of LTP was incubated with emulsion containing a small percentage of pyrene-CE in the TG core in the absence of the acceptor particles, excimer fluorescence rapidly decreased to the base line, and this change was suppressed when pyrene-CE was diluted with CE in the core. This result may indicate that LTP selectively disrupts pyrene-CE excimer formation on the basis of its selective interaction with the CE molecule over TG in the emulsion system as a putative background mechanism for the selective transfer of CE.

Apolipoprotein A-I↗